Interplay between immune responses to HLA and non-HLA self-antigens in allograft rejection

Abstract

Recent studies strongly suggest an increasing role for immune responses against self-antigens (Ags) which are not encoded by the major histocompatibility complex in the immunopathogenesis of allograft rejection. Although, improved surgical techniques coupled with improved methods to detect and avoid sensitization against donor human leukocyte antigen (HLA) have improved the immediate and short term function of transplanted organs. However, acute and chronic rejection still remains a vexing problem for the long term function of the transplanted organ. Immediately following organ transplantation, several factors both immune and non immune mechanisms lead to the development of local inflammatory milieu which sets the stage for allograft rejection.Traditionally, development of antibodies (Abs) against mismatched donor HLA have been implicated in the development of Ab mediated rejection. However, recent studies from our laboratory and others have demonstrated that development of humoral and cellular immune responses against non-HLA self-Ags may contribute in the pathogenesis of allograft rejection. There are reports demonstrating that immune responses to self-Ags especially Abs to the self-Ags as well as cellular immune responses especially through IL17 has significant pro-fibrotic properties leading to chronic allograft failure. This review summarizes recent studies demonstrating the role for immune responses to self-Ags in allograft immunity leading to rejection as well as present recent evidence suggesting there is interplay between allo-and autoimmunity leading to allograft dysfunction.

Early donor-specific antibodies in lung transplantation: Risk factors and impact on survival

“…[4][5][6] In conclusion, PGD and pre-operative humoral allosensitization promote DSA development after lung transplantation. Prevention of PGD could potentially reduce DSA development.…”

“…It has been suggested previously that patients with a positive crossmatch may sequester their DSA into the lungs. 5 The other 5 patients demonstrated DSA pre-operatively with increasing MFI values post-operatively.…”

Cellular and molecular targeting for nanotherapeutics in transplantation tolerance

“…With the advent of modern immunosuppressive drug therapies, substantial improvements have been made in allograft survival in the past 20 years, though these enhanced clinical outcomes are typically due to short-term graft survival [1]. Chronic graft rejection and dysfunction persist despite long-term immunosuppressive drugs, with only 47-61% of grafts surviving to the 10-year mark [1, 2]. These life-long therapies are often harmful to the transplanted cells/organ and lead to non-specific suppression of the entire host immune system, resulting in patient susceptibility to infection and malignancies [3].…”

The Role of Donor-Specific Antibodies in Acute Cardiac Allograft Dysfunction in the Absence of Cellular Rejection

“…This effect may be exacerbated by the interplay between allo- and autoimmunity in some recipients. (16) Another possible explanation for the group with AAD and AMR without DSA is the absorption of DSA or non-HLA antibodies on to the endothelial surface of the allograft, or the formation of immune complexes of anti-HLA antibodies with soluble circulating HLA antigens. (4,17,18) The detection and clinical significance of such antibodies or complexes remain poorly understood and an important area of further research.…”